TWI670096B - Needleless injection device and use thereof in injection of biological material - Google Patents

Abstract

The invention mainly provides a needle-free injection device, which mainly uses a gas transmission tube, a gas storage barrel, a cylinder, and a piston module as a main introduction component of a pressurized gas, and also includes a specially designed venturi module; Therefore, any of the existing fluid substance accommodating bottles (commonly known as ampoules) can be combined with the needle-free injection device of the present invention to perform the needle-free injection process of the fluid substance using the needle-free injection device. In addition to this, the present invention further proposes a new use of the needle-free injection device for completing a needle-free injection procedure for a biological material. It is worth noting that when the needle-free injection device is applied to the needle-free injection process of the biological material, the oscillating plate of a liquid oscillating groove in the venturi module must be taken out, and alternatively Place a gasket into the liquid oscillating tank. Moreover, the experimental data confirmed that the biological material (fibroblasts) ejected through the needle-free injection device can still have a survival rate of up to 80%.

Description

Needle-free injection device and its use for biological material injection

The present invention relates to the related art of needle-free injection, and more particularly to a needle-free injection device and its use for injecting biological materials.

Cell therapy has been proven to safely and effectively slow down the body's aging and help the body restore health, vitality and physical fitness. Since red blood cells, white blood cells, and platelets contained in blood belong to blood cells, "blood transfusion" is currently the most commonly used cell therapy, and it is carried out all over the world every day.

Currently, the new type of cell therapy implants a suspension of animal cells or tissues into the human body by injection or orally. Clinically, compared with oral cell implantation, injection cell implantation has shown the following advantages: (1) enables cells to rapidly disperse throughout the body; (2) cells do not lack blood during dispersion The supply is damaged; and (3) the cells in suspension are rapidly injected into the body's metabolic system by injection.

However, people usually don't like injections, and some people are even allergic to needles. In view of this, needle-free injection devices were developed to complete drugs or fluid substances. Subcutaneous injection. Figure 1 shows a side cross-sectional view of the skin. As can be seen from Fig. 1, when the syringe 1' is used for subcutaneous injection, the needle of the syringe 1' must be passed through the epidermis 21' and the dermis 22' of the skin 2', and then the drug or fluid substance is injected into the skin through the needle. 'The subcutaneous tissue 23'. Anyone with an injection experience knows that after the needle is removed from the skin 2', there is still a pinhole scar on the skin 21' of the skin 2'. Therefore, for patients who must be given frequent injections, such as diabetic patients, the introduction of needle-free injection devices is a great boon. In addition, as can be seen from FIG. 1, the needle-free injection device 3' will eject the liquid medicine at a high speed in a very small size, so that the liquid medicine can pass through the epidermis 21' and the dermis 22' by its own kinetic energy and then enter the subcutaneous tissue 23'; After the liquid drug enters the subcutaneous tissue 23', it will be distributed along the gap of the tissue fiber, which is beneficial to the body to absorb the drug.

Unfortunately, the currently available water column type needle-free injection device has certain convenience, but about 30% of users have pain, redness and burning after subcutaneous injection with a water column type needle-free injection device. With the phenomenon of bleeding, etc., users who have long-term injection needs have limited acceptance of water-column needle-free injection devices. On the other hand, it must be considered that future needle-free injection devices will be further applied to cell therapy, such as stem cell injection or white blood cell injection; therefore, how to develop a suitable needle-free injection device and the needle-free device The application of injection devices to cell therapy has become a very important topic. In view of this, the inventors of the present invention have tried their best to study the invention, and finally developed a needle-free injection device of the present invention and its use for biological material injection.

The main object of the present invention is to provide a needle-free injection device, which mainly uses a gas transmission tube, a gas storage barrel, a cylinder, and a piston module as main introduction components of pressurized gas, and also includes a specially designed venturi. The module; therefore, any of the existing fluid substance receiving bottles (commonly known as ampoules) can be combined into the needle-free injection device of the present invention to perform the needle-free injection process of the fluid substance using the needle-free injection device.

Another object of the present invention is to provide a new use of the needle-free injection device, particularly the use of the needle-free injection device for completing a needle-free injection procedure for a biological material. It is worth noting that when the needle-free injection device is applied to the needle-free injection process of the biological material, the oscillating plate of a liquid oscillating groove in the venturi module must be taken out, and alternatively Place a gasket into the liquid oscillating tank. Moreover, the experimental data confirmed that the biological material (fibroblasts) ejected through the needle-free injection device can still have a survival rate of up to 80%. Moreover, the surviving fibroblasts have a survival rate of more than 90% after receiving subsequent transplanting and culturing.

In order to accomplish the above object of the present invention, the inventor of the present invention provides an embodiment of the needle-free injection device, comprising: a gas storage barrel for storing a pressurized gas, and having a first connection port and a first a second connecting port; a cylinder having a third connecting port and a through port, and the third connecting port is connected to the first connecting port; a piston module is disposed in the cylinder and includes a piston and a piston driving member; wherein one end of the piston is exposed outside the cylinder through the opening, and the piston driving member is connected; The tube module comprises: a venturi tube connected to the second connection port of the gas storage barrel by an inlet port thereof, and having an air outlet; a liquid oscillation groove formed on the venturi And a through hole is formed in the liquid oscillating groove and an oscillating plate is disposed; wherein the through hole communicates with the inside of the venturi; a fixing seat is connected to the liquid oscillating groove for accommodating a liquid a tank is fixed on the liquid oscillating tank; and a groove is formed on the venturi to place a driving circuit board, and the driving circuit board is electrically connected to the oscillating plate; Connecting to the piston driving member and having an air outlet; a gas transmission tube connecting the triggering member for discharging a pressurized gas through the air outlet of the trigger member to drive the piston driving member to push the piston to move Inside the cylinder; a cable Group, based electrically connected to the driving circuit board to supply power to the driving circuit board; and an electrical connection interface between the cable and the driving set is electrically connected to a circuit board module, as based.

<present invention>

1‧‧‧ needleless injection device

C‧‧‧shell

BC‧‧‧ bottom cover

SC‧‧‧Nozzle cover

SOC‧‧‧Nozzle cover

10‧‧‧ gas storage barrel

11‧‧‧Cylinder

13‧‧‧Piston module

14‧‧‧ Venturi tube module

15‧‧‧trigger

16‧‧‧ gas transmission tube

17‧‧‧ cable set

18‧‧‧ bracket

19‧‧‧Electrical connection module

101‧‧‧ first connection

102‧‧‧second connection

111‧‧‧ third connection

112‧‧‧ mouth

CM‧‧‧Connecting parts

132‧‧‧Piston

131‧‧‧Piston drive parts

141‧‧ ‧ Venturi tube

142‧‧‧Liquid oscillating tank

143‧‧‧ fixed seat

144‧‧‧Place slot

FB‧‧‧Fixed parts

1411‧‧‧ inlet

1412‧‧‧ gas outlet

1421‧‧‧through hole

1422‧‧‧Oscillator

18‧‧‧ bracket

181‧‧‧ horizontal board

182‧‧‧ vertical board

183‧‧‧ openings

1811‧‧‧ Carrying Department

CFO‧‧‧ front opening

CRO‧‧‧opening

151‧‧‧ Vents

161‧‧‧Micro-diameter tube

BR‧‧‧ bottom groove

CBO‧‧‧ bottom opening

171‧‧‧Electrical connectors

CSO‧‧‧ side opening

CB‧‧‧ control button

PD‧‧‧shims

PD1‧‧‧ injection hole

OPD‧‧‧ ring pad

S1-S4‧‧‧ steps

2‧‧‧Fluid material storage bottle

<知知>

1'‧‧‧Syringe

2’‧‧‧ skin

21’‧‧‧skin

22’‧‧‧ Genuine leather

23’‧‧‧Subcutaneous organization

3'‧‧‧ Needle-free injection device

Figure 1 is a side cross-sectional view showing the skin; Figure 2 is a perspective view of a needle-free injection device of the present invention; Figures 3A and 3B are exploded views showing the external components of a needle-free injection device of the present invention; An exploded view of the internal components of a needleless injection device of the present invention; FIG. 5 is a perspective view showing a gas storage tank, a cylinder, and a piston module; and FIG. 6 is an exploded view showing a part of the venturi module; FIG. A side cross-sectional view showing a venturi tube and a gas storage tank; FIG. 8 is a perspective view showing a gasket, a ring-shaped pad, and a venturi; and FIG. 9 is a view showing a needle-free injection of the needle-free injection device to complete the biological material. Flow chart of the steps of the injection procedure.

In order to more clearly describe a needle-free injection device of the present invention and its use in the injection of biological materials, the preferred embodiments of the present invention will be described in detail below with reference to the drawings.

Structure of needleless injection device

Referring to Figure 2, there is shown a perspective view of a needleless injection device of the present invention. 3A and 3B, an exploded view of the external components of a needleless injection device of the present invention is shown. Referring again to Figure 4, there is shown an exploded view of the internal components of a needleless injection device of the present invention. According to the design of the present invention, the needle-free injection device 1 comprises: a casing C, a bottom cover BC, a nozzle cover SC, and a nozzle cover. SOC, a gas storage tank 10, a cylinder 11, a piston module 13, a venturi module 14, a trigger member 15, a gas transmission tube 16, a cable set 17, a bracket 18, and an electrical The air module 10, the air cylinder 11, the piston module 13, the venturi module 14, and the electrical connection module 19 are housed in the casing C.

Please refer to FIG. 5 at the same time, which is a perspective view of the gas storage tank, the cylinder, and the piston module. In the assembly of the needle-free injection device 1, the gas storage tank 10 is configured to store a pressurized gas and has a first connection port 101 and a second connection port 102. In addition, the cylinder 11 has a third connecting port 111 and a through port 112, and communicates with the first connecting port 101 of the air tank 10 with its third connecting port 111. It is to be noted that a connecting member CM is disposed between the first connecting port 101 and the third connecting port 111 for connecting the first connecting port 101 and the third connecting port 111 to each other. On the other hand, the piston module 13 is disposed in the cylinder 11 and includes a piston 132 and a piston driving member 131. One end of the piston 131 is exposed outside the cylinder 11 via the opening 112. And connecting the piston driving member 132.

The conventional "double-barrel" needle-free injection system, for example, the needle-free injection system disclosed in Taiwan Patent No. I532511, injects a liquid substance into the Venus by means of a main pressurized gas pushing a push-rod injector. Inside the tube, a droplet of liquid material in the venturi is then atomized by a pressurized gas and introduced into the venturi. Different from the conventional dual-pressure needle-free injection system, the present invention particularly uses the gas transmission tube 16, the gas storage barrel 10, the cylinder 11 and the piston module 13 as the main introduction components of the pressurized gas, and at the same time, the Wenzhou is specially designed. The tube module 14 is constructed such that any of the existing fluid substance containing bottles 2 (commonly known as ampoules) can be combined into the needle-free injection device 1 of the present invention. As shown in Figure 4, the text The tube module 14 mainly includes a venturi tube 141, a liquid oscillating groove 142, a fixing seat 143, a placing groove 144, and a fixing member FB.

Please refer to Figure 6 at the same time, which shows an exploded view of some components of the venturi module. Also, please refer to FIG. 7 at the same time, which is a side cross-sectional view showing the venturi and the gas storage tank. According to the design of the present invention, the venturi 141 has an air inlet 1411 and an air outlet 1412, and the air inlet 1411 is connected to the second connection port 102 of the air tank 10. It is to be noted that the liquid oscillating groove 142 is formed on the venturi 141. The liquid oscillating groove 142 defines a through hole 1421 for connecting the inside of the venturi 141, and an oscillating plate 1422. It is placed in the liquid oscillation groove 142 and covers the through hole 1421. At the same time, the present invention specifically designs the bracket 18 for supporting and fixing the venturi 141. The bracket 18 mainly includes a horizontal plate 181 and a vertical plate 182. As shown, the horizontal plate 181 has a bearing portion 1811, and the vertical plate 182 is coupled to the horizontal plate 181, and an opening 183 is formed at the junction of the horizontal plate 181 and the vertical plate 182.

In the above description, the venturi tube 141 is placed on the carrying portion 1811 of the horizontal plate 181, and the air inlet 1411 is connected to the second connecting port 102 through the opening 183; and the placing slot 144 is The drive circuit board is located within the opening 183. On the other hand, the fixing base 143 is connected to the liquid oscillating groove 142 for fixing a fluid substance accommodating bottle 2 to the liquid oscillating groove 142. It should be noted that the fixing base 143 is exposed through a front opening CFO of the casing C. At the same time, the present invention more specifically designs a fixing member FB for fixing a fluid substance receiving bottle 2 to the fixing. Above the seat 143. In addition, a ferrule 144 is formed on the venturi 141 for placing a driving circuit board, so that the driving circuit board is electrically connected to the vibration in the liquid oscillating groove 142. Slate 1422. According to the design of the present invention, the thickness of the oscillating plate 1422 is between 20 μm and 60 μm; and the oscillating plate 1422 has a plurality of micropores, and the pore size of the micropores is less than 25 μm.

Reference is continued to Figures 2, 3A, 3B, and 4 . According to the design of the present invention, the trigger member 15 enters the inside of the casing C via a rear opening CRO of the casing C, thereby connecting the piston driving member 131. In addition, a gas inlet end of the gas transmission tube 16 is formed with a micro-diameter tube 161 for penetrating into an air outlet 151 of the trigger member 15. In this way, the gas transfer pipe 16 can discharge the pressurized gas through the air outlet 151 of the trigger member 15 to drive the piston drive member 131 to push the piston 132 to move inside the cylinder 11. In the present invention, the cable set 17 is electrically connected to the driving circuit board, and the electrical connecting module 19 serves as an electrical connection interface between the cable set 17 and the driving circuit board. Therefore, the housing C further includes a bottom recess BR, and the bottom recess BR has a bottom opening CBO for connecting an electrical connector 171 of the cable set 17 through the bottom opening CBO. Sexual connection module 19. Furthermore, a bottom cover BC is coupled to the bottom recess BR of the housing C for covering the electrical connector 171 of the cable set 17. In addition, the housing C further includes a side opening CSO for electrically connecting a control button CB to the electrical connection module 19 through the side opening CSO.

New use of needle-free injection devices

A known use of the needle-free injection device 1 of the present invention is to complete a needle-free injection procedure for a fluid substance. When the needle-free injection process of the fluid substance is completed, the oscillation plate 1422 is placed in the liquid oscillation groove 142 above the venturi 141, and the oscillation piece is placed. The 1422 is electrically connected to a drive circuit board placed in the placement slot 144. The fluid substance may be DNA, RNA, DNA coated with nano gold, RNA coated with nano gold, vaccination, collagen, hyaluronic acid or the like. Further, with respect to this needleless injection device 1, the present invention proposes its novel use. In a new application, the needle-free injection device 1 can be applied to complete a needle-free injection procedure for a biological material. It is to be noted that when applied to the needle-free injection process of the biological material, the oscillating plate 1422 within the liquid oscillating groove 142 must be taken out and replaced with a spacer PD and a ring pad OPD.

Figure 8 is a perspective view showing a gasket, a ring pad, and a venturi. According to the design of the present invention, the spacer PD is disposed between the mouth of the fluid substance accommodating bottle 2 and the liquid oscillating groove 142, and has an injection hole PD1 corresponding to the through hole 1421; and, the spacer PD The aperture system is between 0.5 mm and 1.5 mm. On the other hand, the annular pad OPD is disposed between the spacer PD and the liquid oscillation groove 142.

Figure 9 is a flow chart showing the steps of applying the needle-free injection device to complete the needle-free injection procedure of biological material. The needle-free injection device 1 of the present invention can perform the needle-free injection application of the biological material by the following plurality of execution steps: Step (S1): formulating the biological material into a culture liquid to accommodate the fluid substance In the bottle 2; wherein the biological material may be any one of: a cell, a microbial strain, an animal tissue culture, or a plant tissue culture; and the step (S2): pumping up the venturi module 14 The oscillating plate 1422, the spacer PD and the annular pad OPD are placed in the liquid oscillating groove 142, and then the fluid substance accommodating bottle 2 is assembled onto the fixing base 143; Step (S3): based on the air pressure of 20-50 psi, the gas transmission pipe 16 outputs a pressurized gas through the air outlet 151 of the trigger member 15 for driving the piston driving member 132 to push the piston 131 to move to the cylinder. 11 inside, and further, a pressure change inside the cylinder 11 pushes a droplet of the biological suspension entering the venturi 141 through the injection hole PD1 and the through hole 1421; and the step (S4): the creature The droplet of the suspension is injected onto a target via the nozzle cover SC, and the biological material contained in the droplet of the biological suspension injected into the target has a survival of more than 80%. rate.

Experimental example of a new type of use without a needle injection device

In order to confirm that the needle-free injection device 1 of the present invention can be applied to a needle-free injection procedure for completing a biological suspension, the inventors of the present invention have completed several experiments.

The inventor of the case first completed experiment one. In Experiment 1, fibroblasts (HLF FC-0049) were cultured in a minimal essential medium (MEM) to a density of 1.0 x 10 ⁵ cells/mL. Next, the culture solution of the fibroblasts was injected into a 15 mL centrifuge tube by the needle-free injection device 1 of the present invention, and then the cell number and survival rate of the fibroblasts contained in the suspension in the centrifuge tube were calculated using a cell counter. The experimental data is organized in the following table (1) and table (2).

As can be seen from Tables (1) and (2), when the oscillating piece 1422 is not taken out, the culture solution is directly injected into the centrifuge tube using the needle-free injection device 1, and it is found that the culture solution cannot pass through the oscillating piece 1422. In contrast, after the oscillating piece 1422 is taken out and the spacer PD is placed in the liquid oscillating groove 142, the culture solution is injected into the centrifuge tube using the needle-free injection device 1, and the survival rate of the fibroblast is found to follow. The set pressure value rises and decreases. Therefore, the experimental data of Experiment 1 confirms that when the needle-free injection device 1 of the present invention is applied to the needle-free injection process of the biological material, it is necessary to first take out the oscillation piece 1422 in the liquid oscillation groove 142 and replace it. A spacer PD and a ring pad OPD are placed sexually.

The inventor of the case then completed experiment two. In Experiment 2, fibroblasts (HLF FC-0049) were cultured in a minimal essential medium (MEM) to a density of 5.0 x 10 ⁵ cells/mL. Next, the culture solution of the fibroblasts was injected into a 15 mL centrifuge tube by the needle-free injection device 1 of the present invention, and then the cell number and survival rate of the fibroblasts contained in the suspension in the centrifuge tube were calculated using a cell counter. Continuing, the cell suspension collected from the centrifuge tubes of each experimental group was transferred to a 6-well plate, and after 24 hours of culture, the cell attachment of each experimental group was observed under a microscope. Next, for the experimental group with good cell attachment status, that is, the Con group, the A4 group, the A5 group, the A6 group, and the B4 group, the cells in the culture plate were laid down with Trypsin, and then the fibroblasts were counted using a cell counter. Cell number, survival rate, and recovery rate. The experimental data is organized in the following table (3) and table (4).

As can be seen from the table (3), the number of shots of the needle-free injection device 1 and the aperture value of the spacer PD do not affect the survival rate of the fibroblasts injected into the centrifuge tube. Further, as shown in Table (4), the fibroblasts injected into the centrifuge tube were transferred to a 6-well plate for 24 hours, and the Con group, the A4 group, the A5 group, the A6 group, and the B4 group were cultured. The group of fibroblasts showed good adhesion; therefore, compared to the time point of initial transplantation, after 24 After the hour of culture, the number of fibroblasts in the Con group, A4 group, A5 group, A6 group, and B4 group in the culture plate increased significantly, and the calculated cell survival rate was higher than 90%.

Thus, the above-mentioned system has completely and clearly explained all the technical configurations and features of a needle-free injection device of the present invention and its use for biological material injection; and, as described above, the present invention has the following advantages:

(1) The needle-free injection device 1 of the present invention mainly uses a gas transmission pipe 16, a gas storage tank 10, a cylinder 11, and a piston module 13 as main introduction components of pressurized gas, and includes a specially designed Wengen. The tube module 14; therefore, any of the existing fluid substance accommodating bottles 2 (commonly known as ampoules) can be combined into the needle-free injection device 1 of the present invention to complete the absence of the fluid substance by the needle-free injection device 1. Needle injection procedure.

(2) In addition to this, the needle-free injection device 1 of the present invention can also be applied to complete a needle-free injection procedure of a biological material. It should be noted that when applied to the needle-free injection process of the biological material, the oscillating plate 1422 of the liquid oscillating groove 142 in the venturi module 14 must be taken out and replaced one by one. Pad PD and a ring pad OPD. Moreover, the experimental data confirms that the biological material (fibroblasts) ejected by the needle-free injection device 1 of the present invention can still have a survival rate of up to 80%; in addition, the ejected fibroblasts are received and transplanted. After that, its survival rate is higher than 90%.

It is to be understood that the foregoing detailed description of the embodiments of the present invention is not intended to Both should be included in the scope of the patent in this case.

Claims (13)

A needle-free injection device includes: a gas storage barrel for storing a pressurized gas, and having a first connection port and a second connection port; and a cylinder having a third connection port and a port. And the third connecting port is connected to the first connecting port; a piston module is disposed in the cylinder and includes a piston and a piston driving member; wherein one end of the piston is exposed through the opening The venturi tube module includes a venturi tube connected to the second connection port of the gas storage barrel by an air inlet and has an air outlet; a liquid oscillating groove is formed on the venturi, and a through hole is formed in the liquid oscillating groove and an oscillating plate is disposed; wherein the oscillating plate has a thickness of between 20 μm and 60 μm, and the pass a hole is connected to the inside of the venturi; a fixing seat is connected to the liquid oscillating groove for fixing a liquid accommodating tank to the liquid oscillating tank; and a groove is formed in the venturi Above the tube to place a driving circuit board, and the driving power The circuit board is electrically connected to the oscillating plate; a triggering member is connected to the piston driving member and has an air outlet hole; and a fixing member is used for fixing a fluid substance receiving bottle to the fixing seat So that a fluid substance contained in the fluid substance can be dropped into the liquid oscillation tank; a gasket having a pore diameter of between 0.5 mm and 1.5 mm and disposed between the mouth of the fluid material receiving bottle and the liquid oscillating groove, and having an injection hole corresponding to the through hole; a gasket is disposed between the gasket and the liquid oscillating groove; a gas transmission tube is connected to the trigger member for discharging a pressurized gas through the air outlet of the trigger member to drive the piston driving member to push the The piston moves inside the cylinder; a cable set is electrically connected to the driving circuit board to supply power to the driving circuit board; and an electrical connection module is used as the cable set and the driving circuit board An electrical connection interface between the two. The needle-free injection device of claim 1, wherein a communication member is disposed between the first connection port of the air reservoir and the third connection port of the cylinder to enable the first A connection port and the third connection port communicate with each other. The needle-free injection device of claim 1, wherein a gas input end of the gas transfer tube forms a micro-diameter tube for penetrating the vent hole of the trigger member. The needle-free injection device of claim 1, further comprising: a bracket comprising: a horizontal plate having a bearing portion; a vertical plate coupled to the horizontal plate, and an opening formed at a junction of the horizontal plate and the vertical plate; wherein the venturi is placed on the bearing portion of the horizontal plate, and the inlet A port is connected to the second connection port through the opening; and the placement slot and the drive circuit board are located in the opening. The needle-free injection device of claim 4, further comprising: a casing for accommodating the gas storage tank, the cylinder, the piston module, the venturi module, and the An electrical connection module is disposed therein, and the housing is formed with a front opening for exposing the fixing seat to the outside of the housing, and a rear opening for the triggering member to be from the housing The outer portion enters the interior of the housing, and is connected to the piston driving member; one side opening; and a bottom recess having a bottom opening, such that an electrical connector of the cable set connects the electrical property through the bottom opening Connect the module. The needle-free injection device of claim 5, further comprising: a nozzle cover coupled to the front opening of the housing; and a bottom cover coupled to the bottom of the housing a recess to cover the electrical connector of the cable set. The needle-free injection device of claim 5, further comprising: a control button electrically connected to the electrical connection module through the side opening. The needle-free injection device of claim 1, wherein the oscillating plate has a plurality of micropores, and the pore size of the micropores is less than 25 μm. The needle-free injection device of claim 1, which can be applied to complete a needle-free injection procedure of a biological material. The needle-free injection device of claim 9, wherein the biological material can be any of the following: a cell, a microbial strain, an animal tissue culture, or a plant tissue culture. The needle-free injection device of claim 9, wherein a source of the pressurized gas is air. The needle-free injection device of claim 9, wherein the target can be any one of the following: a collection tube, a centrifuge tube, a culture dish, or a skin dressing. The needle-free injection device according to claim 9, wherein the biological material has a density in the culture solution of between 0.5 × 10 ⁵ /ml to 6.0 × 10 ⁵ /ml.